The present invention, “AEROSOL DELIVERY APPARTUS III”, relates to medical-surgical devices designed for improved intrapulmonary deposition of aerosol particles both quantitatively as well as qualitatively in patients on mechanical ventilation via endotracheal tube. Multiple medications readily lend themselves for pulmonary administration. Many diagnostic and therapeutic agents that can be utilized through this route are the bronchodilators, anti-inflammatory agents like steroids, antibiotics, anticholinergics, heparin, surfactant, antiproteases, gene transfer products, insulin, radioactive dyes, etc.
The advantages of intrapulmonary drug delivery as opposed systemic administration are well known. The desired effect at the site of local delivery as opposed to systemic administration minimizes side effects and is the preferred methodology for delivery of several medications. Conventional methods for aerosol delivery have resulted in failure of effective drug delivery to the lungs. They are limited not only in total dose delivery but have also failed to achieve uniform intrapulmonary drug distribution. The two methods currently available for intrapulmonary drug delivery are highly inefficient. They are:
(I). Liquid bolus: The medication is instilled in the form of liquid bolus via a bronchoscope or through an ETT. The distribution by this method is non-uniform. Also there is a significant risk of inducing respiratory distress and hypoxemia.
(II) Aerosol Inhalation: Conventional methods of aerosol drug delivery have employed Metered Dose Inhalers (MDI's) with low boiling point propellants (CFC, HFA) or aerosol particles generated by heat, traditional compressed air nebulizers, or ultrasonic nebulizers. Even though these methods produce aerosol particles in respirable range (<5 microns) compared with the liquid bolus medication, they are limited in total dose delivery and lack-uniform distribution of medication to the lungs. Only a small fraction of the medication reaches the lungs as the majority of the aerosol particles either adhere to the nasal passages and oropharynx or are exhaled out. Efficiency of aerosol delivery drops even further in patients who are intubated and require mechanical ventilation.
Beck et al found that inhalation of nebulized material through an endotracheal tube resulted in deposition of only 1.87% of the delivered particles to the lungs. Methods employing a combined ventilator dispenser and adapter (U.S. Pat. No. 335,175) or other spacer devices with MDI's have revealed equally poor results as most of the aerosol particles adhere to the ETT, the connectors and the inspiratory limb of the corrugated plastic tube.
Investigators over the years have designed numerous endotracheal tubes in an attempt to overcome the hurdles associated with conventional methods of drug delivery to the respiratory system in patients on mechanical ventilation. Most designs of endotracheal tubes so far have only addressed the issue of drug delivery in the form of liquid bolus by incorporating drug irrigation devices in the traditional ETT in the form of secondary canalization with multiple micrometric openings (U.S. Pat. No. 5,146,936).
Factors that influence uniform delivery of aerosol particles in the tracheobronchial tree are the mid-mean diameter of aerosol particles (which should be in the respirable range, i.e. <5 microns), velocity of the aerosol plume, geometry of the aerosol plume (narrow vs. wide), site of the plume generation (proximal to ETT, distal to ETT, or in the lumen of the ETT), orientation of the plume (central vs. eccentric), time of actuation of MDI in the respiratory cycle, temperature and humidity in the respiratory circuit, etc. These features have not been addressed by any of the currently available endotracheal tubes incorporating drug irrigation devices.
U.S. Pat. No. 4,584,998 to McGrail describes an ETT with up to three secondary lumens in addition to the primary lumen in which one lumen can serve the purpose of delivering atomized gases to the patient.
U.S. Pat. No. 4,669,463 to McConnell shows ETT with a secondary lumen in the wall of the main lumen to deliver liquid medication to the respiratory system.
U.S. Pat. No. 4,821,714 to Smelser also describes an ETT with a secondary lumen to deliver medication to the respiratory system. The second lumen splits into two branches that terminate as two orifices, one at the distal tip and other along the exterior wall of the ETT.
U.S. Pat. No. 5,504,224 to Anne M. Buret, Pam Jeblenski, and Robert A. Virag describes an ETT with a secondary lumen in the wall of the ETT that terminates at a perforation (Murphy eye). The single stream of medication splits when it impacts on the distal edge of the opening resulting in delivery of medication both internally and externally of the ETT.
U.S. Pat. No. 5,642,730 to George Baran later continued as U.S. Pat. No. 6,079,413 assigned to the same inventor describes a catheter system for delivery of aerosolized medicine for use with pressurized propellant canister. The system includes an extension catheter that has a length such that the proximal end is connected to the canister and the distal end is positioned in the primary lumen or secondary lumen of the ETT beyond its distal end in the respiratory system. The system is not practical for many reasons. The invention describes an extremely complex system for centering the device in the lumen of the ETT which would require a significant amount of time to be spent in the tracheobronchial tree prior to delivery of medication. Hence, there would be interference with the ventilatory function and increased airway resistance at the time of manipulation of the device in the tracheobronchial tree. Secondly the system is complex enough to require a highly trained member of the professional staff, especially MD to carry out the operation. This may not be possible as currently all methods of drug delivery to tracheobronchial tree in patients on mechanical ventilation require either nursing staff or respiratory therapists and not necessarily MD's. Thirdly the system for prevention of impaction losses, especially carinal impaction is extremely expensive and there is no data demonstrates that the system will function effectively. Overall the system described in the invention is not of any practical clinical utility and hence it is currently being used as an experimental tool in research laboratories.
U.S. Pat. No. 5,964,223 assigned to George Baran describes a nebulizing catheter system similar to U.S. Pat. No. 5,642,730. This system describes the flow of liquid medication through the lumen of a catheter which is nebulized at its tip by a flow of pressurized gas through a coaxial lumen.
U.S. Pat. Nos. 5,579,758, 5,594,987, 5,606,789, 5,513,630, 5,542,412, 5,570,686 show a delivery device for intratracheal administration of drug in aerosol form called ‘Penn Century Intratracheal Aerosolizer (Microsprayer)’ The clinical utility of this device in humans at this time is extremely limited because of its high cost and need for sterilization after every use and as such it is solely being used as a research tool.
In summary, none of the prior art medical devices provide means for effective local delivery of medication to the tracheobronchial tree of both lungs in a cost effective manner.